HDAC6 inhibitors and uses thereof

Abstract

Histone deacetylases 6 (HDAC6) inhibitors and compositions containing the same. Methods of treating diseases and conditions wherein inhibition of HDAC6 provides a benefit, like a cell proliferative disease, an autoimmune or inflammatory disorder, a neurodegenerative disease, a viral disease, malaria, or a combination thereof.

What is claimed is: 
     
       1. A compound of formula I, or a stereoisomer, tautomer, racemic, prodrug, salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
         wherein: 
         ring 
       
       
         
           
           
               
               
           
         
       
       is a five- or six-membered ring wherein one of A, B, C and D is S, S═O, or SO 2  and the remaining are a direct bond or CH 2 ;
 Y is alkylene or arylene; 
 R is selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, aryl, OR′, SR′, NR′R″, and P(O)(OR′)(OR″); and 
 R′ and R″ are independently selected from the group consisting of H, alkyl, and aryl. 
 
     
     
       2. The compound according to  claim 1 , wherein
 ring 
 
       
         
           
           
               
               
           
         
       
       is a six-membered ring wherein one of A, B, C and D is S or SO 2  and the remaining are CH 2 ;
 Y is arylene; 
 R is selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, aryl, OR′, SR′, NR′R″, and P(O)(OR′)(OR″); and 
 R′ and R″ are independently selected from the group consisting of H, alkyl, and aryl. 
 
     
     
       3. The compound according to  claim 1 , wherein the compound has one of the formulas II-VI 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein R is selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, aryl, OR′, SR′, NR′R″, and P(O)(OR′)(OR″); and 
         n is an integer of 0 to 10. 
       
     
     
       4. The compound according to  claim 1 , wherein R is hydrogen or halogen. 
     
     
       5. The compound according to  claim 1 , selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
       6. A composition comprising a compound according to  claim 1 , and one or more pharmaceutically acceptable carriers, diluents and/or excipients. 
     
     
       7. The composition according to  claim 6 , further comprising an adjuvant and/or an anticancer agent. 
     
     
       8. The composition according to  claim 6 , wherein said composition is in a form suitable for oral, parenteral or topical administration, administration by inhalation, by a skin patch, by an implant or by a suppository. 
     
     
       9. The compound of  claim 1 , wherein one of A, B, C, and D is S═O or SO 2  and the remaining are CH 2  or a direct bond. 
     
     
       10. A method for inhibiting a histone deacetylase (HDAC) in a subject in need thereof, said method comprising administering a compound according to  claim 1  to said subject. 
     
     
       11. The method according to  claim 10  wherein the subject has an HDAC-associated disease selected from the group consisting of a cell proliferative disease, an autoimmune disease, an inflammatory disorder, a neurodegenerative disease, a viral disease, malaria, or a combination thereof. 
     
     
       12. The method according to  claim 10  wherein the subject has a cell proliferative disease. 
     
     
       13. The method according to  claim 12 , wherein the cell proliferative disease is cancer, or metastasis thereof. 
     
     
       14. A method for treating a cancer in a subject in need thereof, said method comprising administering a compound according to  claim 1  to said subject.